Dietary Strategies and Novel Pharmaceutical Approaches Targeting Serum ApoA-I Metabolism: A Systematic Overview

Table 10

Summary of the pharmacological approaches targeting apoA-I metabolism in humans.

First author, year	Infusion	Duration	Model	Dose	Effect
Bloedon et al. (2008) [148]	D-4F	A single dose	Coronary artery diseased patients	30 versus 100 versus 300 versus 500 mg	(i) anti-inflammatory activity of HDL
Nissen et al. (2003) [149]	ApoA-I Milano	One infusion for 5 weeks	Patients with acute coronary syndromes	15 versus 45 mg/kg	(i) 15.1 mm^3 and 12.6 mm^3 in atheroma volume
Kempen et al. (2016) and Kallend et al. (2016) [150, 151]	ApoA-I Milano	5 doses during 2 hours	Patients with stable coronary artery disease	10 versus 20 versus 30 versus 40 mg/kg	(i) Dose-dependent in apoA-I concentrations; (ii) Dose-dependent shift from small- to large-sized HDL particles.; (iii) in ABCA1-mediated cholesterol efflux
Nicholls (2016) [152]	ApoA-I Milano	5 weekly doses	120 patients with a recent acute coronary syndrome	20 mg/kg	(i) 7.8 and 5.3% in fasting HDL-C and apoA-I concentrations; (ii) No effects on percent and total atheroma volume
Nicholls (2007) [152]	CSL-111	Once a week for a month	Patients elected for coronary angiography	40 versus 80 mg/kg	(i) Abnormalities in liver function test; (ii) 3.4% in atheroma volume
Easton et al. (2014) and Gille et al. (2014) [153, 154]	CSL112	A single dose	Healthy volunteers	5 versus 15 versus 40 versus 70 versus 105 versus 135 mg/kg	(i) in apoA-I concentrations for 3 days or longer; (ii) 81% in HDL concentrations; (iii) pre-β-HDL particle concentrations; (iv) 2.9-fold in cholesterol efflux
Easton et al. (2014) and Gille et al. (2014) [153, 154]	CSL112	Once or twice weekly for 4 weeks	Healthy volunteers	3.4 versus 6.7 g once a week versus 3.4 g twice a week	(i) in apoA-I concentrations for 3 days or longer; (ii) pre-β-HDL particle concentrations; (iii) 2.6-fold in cholesterol efflux
Tricoci et al. (2015) [155]	CSL112	A single dose	Patients with atherosclerosis	1.7 versus 3.4 versus 6.8 g	(i) No elevations in alanine aminotransferase or aspartate aminotransferase; (ii) No serious adverse events.; (iii) Dose-dependent in apoA-I concentrations and total cholesterol efflux
Gibson et al. (2016) [156]	CSL112	4 weekly infusions	Patients with myocardial infarction	0 versus 2 versus 6 g	(i) Safe for use; (ii) Dose-dependent in fasting apoA-I, HDL-C concentrations and cholesterol efflux
Tardif (2014) [157]	CER-001	6 weekly infusions	Patients with acute coronary syndromes	3 versus 6 versus 12 mg/kg	(i) No changes in atheroma volumes
Kootte et al. (2015) [158]	CER-001	9 infusions twice weekly for 28 days	Patients with familial hypoalphalipoproteinemia	8 mg/kg	(i) 94% in apoA-I concentrations; (ii) 117% in HDL-C concentrations; (iii) 8.8% atherosclerotic lesion size; (iv) 44% in cholesterol efflux; (v) fecal neutral sterol excretion
Hovingh et al. (2015) [159]	CER-001	12 infusions twice weekly	Patients with homozygous familial hypercholesterolemia	8 mg/kg	(i) 13% in apoA-I; (ii) 2.8% in vessel wall; (iii) Trend toward in vessel wall thickness
Zheng et al. (2016) [160]	CER-001	A single dose	Patients with atherosclerotic carotid artery disease	3 mg/kg	(i) 8.7% in apoA-I; (ii) 13.8% in the cholesterol efflux capacity
Nicholls et al. 2017 [161]	CER-001	10 weekly infusions	Coronary artery diseased patients		(i) No difference in atheroma volume; (ii) No difference in LDL-C
Bloedon et al. (2008) [148]	D-4F	A single dose	Coronary artery diseased patients	30 versus 100 versus 300 versus 500 mg	(i) anti-inflammatory activity of HDL
Bailey et al. (2010) [162]	RVX-208	7 days	Healthy subjects	1 to 20 mg/kg/day	(i) 11% in apoA-I concentrations; (ii) 11% in HDL-C concentrations; (iii) 42% in pre-β1-HDL concentrations; (iv) 11% in ABCA1-mediated cholesterol efflux
Nicholls et al. (2011) [163]	RVX-208	Twice daily for 12 weeks	Patients with stable coronary artery disease	50 versus 100 versus 150 mg	(i) No difference in apoA-I concentrations
Gilham et al. (2016) [164]	RVX-208	24 weeks	Statin-treated patients with low HDL-C concentrations	200 mg/day	(i) in apoA-I concentrations; (ii) HDL particle number; (iii) Safe for oral use
Nicholls et al. (2016) [32]	RVX-208	26 weeks	Statin-treated patients with coronary artery disease and low HDL-C concentrations	100 mg twice daily	(i) No difference in atheroma volume, HDL-C, and apoA-I concentrations
Siebel et al. (2016) [165]	RVX-208	29–33 days	20 males with prediabetes	100 mg	(i) No change in HDL-C and apoA-I concentrations; (ii) 11% in medium size HDL particles; (iii) 10% in small size HDL particles; (iv) Later and glucose peak; (v) endogenous glucose production
Shamburek et al. (2016) [166]	Recombinant human lecithin-cholesterol acyltransferase infusion	7 months	1 patient with familial lecithin-cholesterol acyltransferase deficiency	Optimization phase: 3 times, 1 hour, 0.3, 3.0, and 9.0 mg/kg.; Maintenance phase: every 1 to 2 weeks, 3.0 or 9.0 mg/kg	(i) apoA-I, HDL-C, and to a lesser extent LDL-C; (ii) postprandial triacylglycerol concentrations

Percentages calculated from the mean values.